To explore the pharmacological mechanism of action using digital twin

With the advent of medical technology and science, the number of animals used in research has increased. For decades, the use of animals in research and product testing has been a point of conflict. Experts and pharmaceutical manufacturers are harming animals worldwide during laboratory research. Animals have also played a significant role in the advancement of science; animal testing has enabled the discovery of various novel drugs. The misery, suffering, and deaths of animals are not worth the potential human benefits. As a result, animals must not be exploited in research to assess the drug mechanism of action (MOA). Apart from the ethical concern, animal testing has a few more downsides, including the requirement for skilled labor, lengthy processes, and cost. Because it is critical to investigate adverse effects and toxicities in the development of potentially viable drugs. Assessment of each target will consume the range of resources as well as disturb living nature. As the digital twin works in an autonomous virtual world without influencing the physical structure and biological system. Our proposed framework suggests that the digital twin is a great reliable model of the physical system that will be beneficial in assessing the possible MOA prior to time without harming animals. The study describes the creation of a digital twin to combine the information and knowledge obtained by studying the different drug targets and diseases. Mechanism of Action using Digital twin (MOA-DT) will enable the experts to use an innovative approach without physical testing to save animals, time, and resources. DT reflects and simulates the actual drug and its relationships with its target, however presenting a more accurate depiction of the drug, which leads to maximize efficacy and decrease the toxicity of a drug. In conclusion, it has been shown that drug discovery and development can be safe, effective, and economical in no time through the combination of the digital and physical models of a pharmaceutical as compared to experimental animals.

Potentially Toxic Elements’ Contamination of Soils Affected by Mining Activities in the Portuguese Sector of the Iberian Pyrite Belt and Optional Remediation Actions: A Review

Both sectors of the Iberian Pyrite Belt, Portuguese and Spanish, have been exploited since ancient times, but more intensively during and after the second half of the 19th century. Large volumes of polymetallic sulfide ore were extracted in open pits or in underground works, processed without environmental concerns, and the generated waste rocks and tailings were simply deposited in the area. Many of these mining sites were abandoned for years under the action of erosive agents, leading to the spread of trace elements and the contamination of soils, waters and sediments. Some of these mine sites have been submitted to rehabilitation actions, mostly using constructive techniques to dig and contain the contaminated tailings and other waste materials, but the remaining soil still needs to be treated with the best available techniques to recover its ecosystem functions. Besides the degraded physical structure and poor nutritional status of these soils, they have common characteristics, as a consequence of the pyrite oxidation and acid drainage produced, such as a high concentration of trace elements and low pH, which must be considered in the remediation plans. This manuscript aims to review the results from studies which have already covered these topics in the Iberian Pyrite Belt, especially in its Portuguese sector, considering: (i) soils’ physicochemical characteristics; (ii) potentially toxic trace elements’ concentration; and (iii) sustainable remediation technologies to cope with this type of soil contamination. Phytostabilization, after the amelioration of the soil’s properties with organic and inorganic amendments, was investigated at the lab and field scale by several authors, and their results were also considered.

Decellularized Colorectal Cancer Matrices as Bioactive Scaffolds for Studying Tumor-Stroma Interactions

More than a physical structure providing support to tissues, the extracellular matrix (ECM) is a complex and dynamic network of macromolecules that modulates the behavior of both cancer cells and associated stromal cells of the tumor microenvironment (TME). Over the last few years, several efforts have been made to develop new models that accurately mimic the interconnections within the TME and specifically the biomechanical and biomolecular complexity of the tumor ECM. Particularly in colorectal cancer, the ECM is highly remodeled and disorganized and constitutes a key component that affects cancer hallmarks, such as cell differentiation, proliferation, angiogenesis, invasion and metastasis. Therefore, several scaffolds produced from natural and/or synthetic polymers and ceramics have been used in 3D biomimetic strategies for colorectal cancer research. Nevertheless, decellularized ECM from colorectal tumors is a unique model that offers the maintenance of native ECM architecture and molecular composition. This review will focus on innovative and advanced 3D-based models of decellularized ECM as high-throughput strategies in colorectal cancer research that potentially fill some of the gaps between in vitro 2D and in vivo models. Our aim is to highlight the need for strategies that accurately mimic the TME for precision medicine and for studying the pathophysiology of the disease.

Extremely Metal-Poor Asymptotic Giant Branch Stars

Little is known about the first stars, but hints on this stellar population can be derived from the peculiar chemical composition of the most metal-poor objects in the Milky Way and in resolved stellar populations of nearby galaxies. In this paper, we review the evolution and nucleosynthesis of metal-poor and extremely metal-poor (EMP) stars with low and intermediate masses. In particular, new models of 6 M⊙ with three different levels of metallicity, namely Z=10−4, 10−6 and 10−10, are presented. In addition, we illustrate the results obtained for a 2 M⊙, Z=10−5 model. All these models have been computed by means of the latest version of the FuNS code. We adopted a fully coupled scheme of solutions for the complete set of differential equations describing the evolution of the physical structure and the chemical abundances, as modified by nuclear processes and convective mixing. The scarcity of CNO in the material from which these stars formed significantly affects their evolution, their final fate and their contribution to the chemical pollution of the ISM in primordial galaxies. We show the potential of these models for the interpretation of the composition of EMP stars, with particular emphasis on CEMP stars.

Flowing Refractometer for Feed Water State Control in the Second Loop of Nuclear Reactor

The necessity to control the feed water state in the second loop of a nuclear power plant nuclear reactor is justified. The different methods of the state control of flowing water in the pipeline are reviewed. It has been established that controlling the feed water state should not result in irreversible changes in its chemical composition and physical structure. A change in the composition or structure of feed water leads to a change in its heat capacity. The heat transfer deteriorates, the production of electrical energy in the installation decreases, and the additional release of heat into the atmosphere increases. This process also occurs during the heat capacity changes for other reasons. The method for controlling the feed water heat capacity by measuring the value of the refractive index n is developed. The design of a flow-through refractometer based on the total internal reflection for control of the feed water state in the stream is made. The dependence of the heat capacity change of feed water from the refractive index is established. The results of research on different types of water are presented.

Triple Crossed Flexure Pivot Based on a Zero Parasitic Center Shift Kinematic Design

Thanks to their absence of play, absence of contact friction and possible monolithic fabrication, flexure pivots offer advantages over traditional bearings in small-scale, high accuracy applications and environments where lubrication and wear debris are proscribed. However, they typically present a parasitic center shift that deteriorates their rotational guidance accuracy. Existing solutions addressing this issue have the drawbacks of reducing angular stroke, prohibiting planar design, or introducing overconstraints or underconstraints. This article introduces a new triple crossed flexure pivot called TRIVOT that has a reduced parasitic center shift without overconstraints nor internal mobility, while allowing either optimal stress distribution in the flexures or a planar design. The new architecture also makes it possible to place the center of rotation outside of the physical structure, which is not the case with traditional bearings. Based on finite element simulations, we show that the parasitic shift is reduced by one order of magnitude in comparison to the widely used crossed flexure pivot. We also derive and validate formulas for the rotational stiffness and angular stroke limit of the TRIVOT. Finally, we show that a high support stiffness can be achieved with a lowest uwanted eignenfrequency 13.5 times higher than the first eigenfrequency. We expect this new pivot to become a competitive alternative to the crossed flexure pivot for applications where high accuracy and compactness are required.

Nurses’ perceptions of counseling and rapid testing for sexually transmitted infections

Objective: to understand Family Health Strategy nurses’ perceptions on counseling and rapid testing for sexually transmitted infections. Methods: this is a qualitative study, with data triangulation. Data collection was conducted through a semi-structured interview with seven nurses from Family Health Strategy. For systematization and data processing, content analysis was adopted in the thematic modality. Results: after analysis, four categories emerged: Rapid test training; Counseling conduction; Ease in rapid testing offer; and Challenges offering rapid testing. Conclusion: nurses’ perceptions were related to difficulties in the face of pre and posttest counseling, requiring improvement, permanent education and training for professional preparation, and the logistics of inputs and materials, in addition to changes in the physical structure of the units.

Indication-based protocols with different solutions for mechanical stromal-cell transfer

Background Regenerative medicine is the fastest developing branch of plastic surgery in recent times. Adipose tissue is one of the largest and most important sources in the body for stromal cells. Although mechanical isolation methods are both very popular and have many advantages, they still have no accepted protocols. Objective We developed new protocols called indication-based protocols (IPs) for standardization and new techniques called mechanical stromal-cell transfer (MEST) by using ultra-sharp blades and dilution of adipose tissue with different solutions (saline, Ringer and 5% Dextrose) Methods & material: In order to obtain the desired physical structure (liquid, gel, solid) and the desired volume, four different types of IPs have been defined. Adipose tissue was prediluted with different solutions using 10 or 20 cc injectors in IPs 1 and 2, while condensed adipose tissue was used directly in IPs 3 and 4. Results In MEST, stromal cells were obtained from 100 mL of condensed fat using different IPs with 92% mean viability and cell counts of 26.80–91.90 × 106. Stromal cells can be obtained in the desired form and number of cells by using four different IPs. Conclusion Isolation of stromal cells by cutting fat with sharp blades will prevent the death of fat tissue and stromal cells and will allow high viability and cell count with our new technique. Predilution with different solutions: Diluting the condensed adipose tissue with the desired solutions (saline, Ringer or 5% Dextrose) before the adinizing process will provide even more stromal cells. Lay Summary Obtaining regenerative stromal cells from adipose tissue can be done by two methods: Enzymatic and mechanical. Mechanical methods have many advantages. Although mechanical stromal cell extraction from adipose tissue is very popular and many techniques have been described, there are still no accepted protocols, definition for the end product, and no consensus on the status of the stromal cells. In this study, stromal cells were obtained mechanically by using ultra-sharp blade systems, without exposing adipose tissue to blunt trauma. Thus, a higher number of cells and higher viability could be obtained. An “Indication based” protocol has been defined for the first time in order to obtain the desired number and status (solid, semi-solid, liquid) end product. Diluting the condensed adipose tissue with the desired solutions (saline, Ringer or 5% Dextrose) before the adinizing process will provide even more stromal cells. This will provide an opportunity for clinicians to obtain and apply a stromal cell solution for different indications in different anatomical regions.

Changes implemented in the work environment of nurses in the COVID-19 pandemic

ABSTRACT Objective: to describe the changes implemented in the work environment of nurses in university hospitals considering the COVID-19 pandemic. Methods: this qualitative and descriptive research was developed from an online survey with 75 nurses from three Brazilian university hospitals. Data processing occurred through textual analysis with the aid of software IRAMUTEQ. Results: five semantic classes were obtained: Organization of units for exclusive care of patients with COVID-19; Adaptations in the use of personal protective equipment; Physical structure adaptation; Care flow institution; Increased number of beds and training courses. Final considerations: the results show the effort of healthcare and nursing professionals/managers in the development of structural adaptations and reorganizations of care processes, in the hospital context, to respond with quality and efficiency to the demands arising from the COVID-19 pandemic.